OSTEOGENESIS

IMPERFECTA AND
OSTEOPOROSIS

OSTEOGENESIS
IMPERFECTA

Comprises a heterogeneous group of heritable

disorders characterized by impairment of
collagen maturation.
It arises due to mutations in one of two genes
that guide the formation of type 1 collagen :
COL 1 A1 gene on chromosome 17 and COL 1
A2 gene on chromosome 7.
Collagen forms a major portion of bone,
dentin,sclerae,ligaments and skin;
osteogenesis imperfecta demonstrate a variety
of changes that involve these sites.

CLINICAL FEATURES

Extreme fragility and porosity of the bones,

with proneness to fracture.

Some affected individuals also have blue sclera

, altered teeth , hypoacusis , long bone and
spine deformities , and joint hyperextensibility.

Many patients also have a tendency towards

capillary bleeding.

Opalescent dentin in patient with

osteogenesis imperfecta

CLASSIFICATION

1.
2.
3.
4.

Based on Sillence et al classification, 4

types of osteogenesis imperfecta exist
TYPE
TYPE
TYPE
TYPE

1
2
3
4

Osteogenesis
Osteogenesis
Osteogenesis
Osteogenesis

imperfecta
imperfecta
imperfecta
imperfecta

TYPE 1 OSTEOGENESIS IMPERFECTA

Most common and mildest form.

Symptoms include blue sclera , in utero
fractures in 10 % of patients , mild to
moderate bone fragility with frequency of
fractures decreasing after puberty ,
hearing loss , easy bruising and short
stature.
It is an autosomal dominant trait.

TYPE 2 OSTEOGENESIS IMPERFECTA

Most severe form.

Exhibits extreme bone fragility and frequent
fractures.
In utero fractures are present in 100% of cases.
Blue sclera may be present , hearing loss is not
common.
Small nose, micrognathia and short trunk may
be present.
Both autosomal recessive and dominant
patterns may occur.

TYPE 3 OSTEOGENESIS IMPERFECTA

Most severe form noted in individuals

beyond the prenatal period.
Sclera of variable hue , limb shortening
and progressive deformities and
pulmonary hypertension.
In utero fractures occur in 50% of cases.
No hearing loss reported in this type.
Both autosomal recessive and dominant
patterns may occur.

TYPE 4 OSTEOGENESIS IMPERFECTA

Associated with mild to moderately severe

bone fragility.
Symptoms include normal sclera, normal
hearing, fractures that begin in infancy and
mild angulation and shortening of long
bones.
The frequency of fractures decreases with
puberty.
This variant is an autosomal dominant trait.

RADIOGRAPHIC
FEATURES

The radiographic hallmarks of

osteogenesis imperfecta include
osteopenia, bowing, angulation or
deformity of the long bones, multiple
fractures and wormian bones ( sutural
bones ) in the skull.
Radiograph typically reveal premature
pulpal obliteration , although shell teeth
rarely may be seen.

HISTOLOGIC FINDINGS

The bone cortex is thin and porous. The bone

trabeculae are thin delicate and widely
separated.
Osteoblastic activity appears retarded and
imperfect and for this reason the thickness of
long bone is deficient.
Failure of woven bone to become transformed
to lamellar bone.
Defective microvascular system and decreased
collagen fibril diameter have been observed.

Microscopic changes of OI

TREATMENT AND PROGNOSIS

There is no cure for OI, thus symptomatic

improvement is the primary goal of
currently available treatment options.
The mainstays of treatment are
PHYSIOTHERAPY, REHABILITATION and
ORTHOPEDIC SURGERY.
The prognosis varies from relatively good
to very poor.

OSTEOPOROSIS

Also known as MARBLE BONE DISEASE ,

ALBERS-SCHONBERG DISEASE ,
OSTEOSCLEROSIS FRAGILIS GENERALISATA.
It is a rare hereditary bone disease of
heterogeneous pathophysiology in which
failure of osteoclastic bone resorption leads
to increased bone mass.
A German radiologist, Albers- schonberg,
first described osteoporosis in 1904.

ETIOLOGY

The primary underlying defect is failure of

the osteoclasts to resorb bone.
Defective osteoclastic bone resorption ,
combined with continued bone formation
and endochondral ossification , results in
thickening of cortical bone and sclerosis of
the cancellous bone.
Heterogeneous molecular or genetic
defects can result in impaired osteoclastic
function.

CLINICAL FEATURES

Three distinct forms of the disease are based on

age and clinical features ADULT ONSET,
INFANTILE , and INTERMEDIATE.
The infantile and intermediate types have an
autosomal recessive mode of transmission,
while adult onset type shows autosomal
dominant inheritance.
If untreated, infantile type results in death by
first decade of life.
Adult onset type are asymptomatic and have
good long term survival rates.

INFANTILE
OSTEOPOROSIS

Also called MALIGNANT OSTEOPOROSIS.

Diagnosed early in life.
Failure to survive and growth retardation are
symptoms.
Bony defects occur
Nasal stuffiness due to mastoid and paranasal
sinus malformation is often the presenting feature.
Cranial nerve entrapment neuropathies occur.
Manifestations include deafness, proptosis and
hydrocephalus.

Dentition might be delayed.

Bones are fragile and can fracture easily,
osteomyelitis of mandible is common due
to deficient blood supply.
Patients might have anemia, easy
bruising, bleeding, recurrent infections,
hepatospleenomegaly, hypersplenism,
hemolysis, sleep apnea and blindness.

ADULT OSTEOPOROSIS

Also called BENIGN OSTEOPOROSIS.

Diagnosed in late adolescence or adulthood.
Approximately one half of the patients are
asymptomatic and diagnosis is made
incidentally or is based on family history.
Other patients might present with
osteomyelitis or fractures.
Many patients have bone pain.
Bones are fragile and might fracture easily.

Bony defects are common and include

cranial nerve entrapment neuropathies
and osteoarthritis.
40% of patients have recurrent fractures
while osteomyelitis of mandible occur in
10% of patients.
Other manifestations include visual
entrapment, hepatospleenomegaly, short
stature, large head and nystagmus.

RADIOGRAPHIC
FEATURES

Patients usually have generalized osteosclerosis.

The bones might appear club like or show an
appearance of a bone within bone.
Vertebrae are extremely radiodense. They may
show alternating bands, known as the Rugger
jersy sign.
The entire skull is thickened and dense ,
especially at the base.
The roots of the teeth often are difficult to
visualize because of the density of the
surrounding bone.

HISTOPATHOLOGIC FEATURTES

Several patterns of abnormal endosteal

bone formation have been described.These
include the following
Tortuous lamellar trabeculae replacing the
cancellous portion of bone.
Globular amorphous bone deposition in the
marrow spaces.
Osteophytic bone formation.
Numerous osteoclasts may be seen, but
there is no evidence that they function.

TREATMENT AND PROGNOSIS

Calcitriol appears to help by stimulating dormant

osteoclasts and thus stimulating bone
resorption.
Erythropoietin can be used to correct anemia.
Corticosteroids have been used with the hope of
stimulating bone resorption and treating the
anemia.
Treatment with gamma interferon has been
shown to produce long term benefits.
No specific medical treatment exists for the
adult type.